Objective:To investigate the inhibitory effect of curcumin on influenza virus HIN1 and H3N2 in vitro, Methods:The directly killing role of cureumin extract in vitro to influenza virus type A subtype H1N1 and H3N2 wa...Objective:To investigate the inhibitory effect of curcumin on influenza virus HIN1 and H3N2 in vitro, Methods:The directly killing role of cureumin extract in vitro to influenza virus type A subtype H1N1 and H3N2 was evaluated by the canine kidney cells (MDCK), Results:The largest non toxic concentration of curcumin extract was 12, 5g/L and the effective inhibitory concentration to H1N1 and H3N2 was 6, 25G/1 AND 1,56g/L respectively, Conclusion: Curcumin extract have directly killing effect on H1N1 and H3N2 infections.展开更多
[Objective]The aim of this study was to identify transient expression of movement protein (MP) gene in Nicotinana benthaminana rapidly and further investigate the function of this exogenous gene. [Method]The movemen...[Objective]The aim of this study was to identify transient expression of movement protein (MP) gene in Nicotinana benthaminana rapidly and further investigate the function of this exogenous gene. [Method]The movement protein gene of barley yellow dwarf virus (BYDV) was cloned into potato virus X (PVX) viral vector of pGR107,and PVX-recombinant vector was obtained. After electroporation of Agrobacterium tumefaciens,PVX was inoculated into the lower leaves of tobacco by Agrobacterium infiltration assay to observe the infection of virus on tobacco. [Result]After infection for 7 days,upper non-inoculated leaves of tobacco infected by the PVX-recombinant vector showed the virus infection symptoms,while the control group had no viral infection phenomenon. Daily follow-up observations for two groups revealed that tobacco infected by PVX-recombinant vector had severe symptoms of virus infection and curling leaves,or even led to necrosis both in infiltrated and systemic leaves in late period. However,tobacco infected by PVX vector had only slight symptoms of virus infection and could recover from infection. RT-PCR of the infected tobacco indicated that exogenous gene BYDV-MP had a normal transcription and expression in tobacco. [Conclusion]As a determinant factor for viral disease,BYDV-MP promotes the systemic infection rate of PVX and its symptom. In addition,it is feasible to express exogenous MP gene in Nicotiana benthaminan via PVX expression vector.展开更多
AIM: To assess the combinative role of aflatoxin B1 (AFB1), cyanobacterial toxins (cyanotoxins), and hepatitis B virus (HBV) x gene in hepatotumorigenicity. METHODS: One-week-old animals carrying HBV x gene an...AIM: To assess the combinative role of aflatoxin B1 (AFB1), cyanobacterial toxins (cyanotoxins), and hepatitis B virus (HBV) x gene in hepatotumorigenicity. METHODS: One-week-old animals carrying HBV x gene and their wild-type littermates were intraperitoneally (ip) injected with either single-dose AFB1 [6 mg/kg body weight (bw)], repeated-dose cyanotoxins (microcystin- LR or nodularin, 10 μg/kg bw once a week for 15 wk), DMSO (vehicle control) alone, or AFB1 followed by cyanotoxins a week later, and were sacrificed at 24 and 52 wk post-treatment. RESULTS: AFB1 induced liver tumors in 13 of 29 (44.8%) transcjenic mice at 52 wk post-treatment, significantly more frequent than in wild-type mice (13.3%). This significant difference was not shown in the 24-wk study. Compared with AFB1 exposure alone, MC-LR and nodularin yielded approximately 3-fold and 6-fold increases in the incidence of AFB1-induced liver tumors in wild-type animals at 24 wk, respectively. HBV x gene did not further elevate the risk associated with coexposure to AFB1 and cyanotoxins. With the exception of an MC-LR-dosed wild-type mouse, no liver tumor was observed in mice treated with cyanotoxins alone at 24 wk. Neither DMSO-treated transgenic mice nor their wild-type littermates had pathologic alterations relevant to hepatotumorigenesis in even up to 52 wk. CONCLUSION: HBV x gene and nodularin promote the development of AFB1-induced liver tumors. Co-exposure to AFB1 and MC-LR tends to elevate the risk of liver tumors at 24 wk relative to exposure to one of them. The combinative effect of AFB1, cyanotoxins and HBVx on hepatotumorigenesis is weak at 24 wk.展开更多
Although there were reports suggesting the involvement of endogenous cAMP in plant defense signaling cascades, there is no direct evidence supporting this notion yet and the detailed mechanism is unclear. In the prese...Although there were reports suggesting the involvement of endogenous cAMP in plant defense signaling cascades, there is no direct evidence supporting this notion yet and the detailed mechanism is unclear. In the present study, we have used pathogenic fungi Verticillium dahliae and Arabidopsis plants as a model system of plant-microb interaction to demonstrate the function of endogenous cAMP in Arabidopsis defense responses. Both V. dahliae inoculation and Verticillium toxins injection induced typical “wilt” symptoms in Arabidopsis seedlings. When either 8-Br-AMP (a membrane permeable cAMP analogue) or salicylic acid (SA) was applied to Arabidopsis, the plants became resistant to V. dahliae toxins. However, addition of 8-Br-AMP did not increase the resistance of Arabidopsis transgenic plants deficient in SA to the toxins, suggesting that cAMP might act upstream of SA in plant defense signaling pathway. Indeed, 8-Br-cAMP and forskolin, an activator of adenylyl cyclase, significantly stimulated the endogenous SA level in plants, whereas DDA, an inhibitor of adenylyl cyclase dramatically reduced toxin-induced SA increase. Both the endog- enous cAMP and SA increased significantly in Arabidopsis seedlings treated with toxins. Furthermore, transcription level of pathogenesis-related protein 1 gene (PR1) was strongly induced by both 8-Br-cAMP and the toxin treatment. Taken together, our data demonstrate that endogenous cAMP is involved in plant defense responses against Verticillium- secreted toxins by regulating the production of the known signal SA in plant defense pathway.展开更多
Using mice infected with coxsackie B-3 virus (CVB3) as a viral myocarditis model, we observed the inhibitory effect of Astragalus membranaceus (AM) on CVB3-RNA replication in myocardial tissue of mice by RNA-RNA in si...Using mice infected with coxsackie B-3 virus (CVB3) as a viral myocarditis model, we observed the inhibitory effect of Astragalus membranaceus (AM) on CVB3-RNA replication in myocardial tissue of mice by RNA-RNA in situ hybridization with negative-strand RNA Probes labelled with  ̄(35)S and quantitative imaging analysis of positive signals. The mechanism of its effect on CVB3-RNA replication has been investigated by detection of beta-interferon (β-IFN) as well. Results showed that the copy numbers of CVB3-RNA as well as the histologic scores (necrosis) in myocardial tissues of infected-AM treated mice were significantly lower than those in infected and normal saline treated mice, suggesting that AM could inhibit the replication of CVB3-RVA,but its effect on CVB3-RNA replication had no correlation with induction of β-IFN.展开更多
The cucumber mosaic virus (CMV) isolate P1 caused very mild symptoms on many plant species. After serial passages by mechanical inoculation over five years, CMV P1 caused severe symptoms on several tobacco cultivars a...The cucumber mosaic virus (CMV) isolate P1 caused very mild symptoms on many plant species. After serial passages by mechanical inoculation over five years, CMV P1 caused severe symptoms on several tobacco cultivars and tomato. A specific band of approximately 0.3 kb in length was amplified by RT PCR with primers synthesized based on reported CMV satellite RNA (satRNA) sequences. Sequence analysis showed there were two satRNAs (Sat P1 1 and Sat P1 2). Sat P1 1 contained 335 nucleotides, and Sat P1 2 contained 394 nucleotides. These two satRNAs shared 64% overall nucleotide sequence homology, and differences between the two satRNAs included mutations as well as deletions. Sat P1 1 was identical to a satRNA (Z96099) reported in 1995 in CMV P1. Based on differences in the sequence and secondary structure between these two satRNAs, we conclude that Sat P1 2 represents the emergence of a new satellite (necrotic satellite) from attenuated satRNA populations. The possible effect of the emergence of this new satRNA is discussed.展开更多
Dose-dependent IgY antibody response to different amounts oforthopox virus (OPV) antigen has been studied in immunized chickens for two different OPV strains (vaccinia virus, 7.0× 10^6 PFU and cowpox virus, 9....Dose-dependent IgY antibody response to different amounts oforthopox virus (OPV) antigen has been studied in immunized chickens for two different OPV strains (vaccinia virus, 7.0× 10^6 PFU and cowpox virus, 9.2× 10^7PFU). The antibody responses to different immunizations were tested and compared by indirect immunofluorescence antibody test. Our results, together with the literature, show that the antigen dose used for immunization plays an important role for the production of specific Abs. An increase in antigen concentration may achieve higher Ab titers but, dependent on the immunogenicity of OPV antigen, it can also lead to an immune depression. However, in this study we found that OPV played a positive correlation between antigen concentration and Ab-titer.展开更多
AIM: To evaluate the anti-viral effect of emodin plus Astragalus polysaccharide (APS) in hepatitis B virus (HBV) transgenic mice.METHODS: Sixty HBV transgenic mice (HBV TGM) whose weight varied between 18 and 24 g wer...AIM: To evaluate the anti-viral effect of emodin plus Astragalus polysaccharide (APS) in hepatitis B virus (HBV) transgenic mice.METHODS: Sixty HBV transgenic mice (HBV TGM) whose weight varied between 18 and 24 g were randomly divided into 3 groups, with 20 mice in each group. Group A was the normal control, where the mice were treated with physiological saline; group B was the positive control where the mice were treated with lamivudine solution (100 mL/kg per day). Group C was the experimental group where the mice were treated with physiological saline containing emodin and APS (57.59 mg/kg per day and 287.95 mg/kg per day, respectively). The mice were treated daily for 3 wk. After 1 wk recovery time, the mice were sacrifi ced and serum as well as liver tissues were collected for ELISA and histological examination.RESULTS: After 21 d treatment, HBV DNA levels in group B and group C significantly declined when compared with group A (P < 0.05). However, a signif icant increase in HBV DNA content was observed in group B, whereas this phenomenon was not observed in group C. A reduction in the contents of HBsAg, HBeAg and HBcAg in the mice from group B and C was observed when compared with group A.CONCLUSION: Emodin and APS have a weak but persistent inhibitory effect on HBV replication in vivo, which may function as a supplementary modality in the treatment of hepatitis B infection.展开更多
An emerging mosquito-borne arbovirus named Zika virus(ZIKV), of the family Flaviviridae and genus Flavivirus, is becoming a global health threat. ZIKV infection was long neglected due to its sporadic nature and mild s...An emerging mosquito-borne arbovirus named Zika virus(ZIKV), of the family Flaviviridae and genus Flavivirus, is becoming a global health threat. ZIKV infection was long neglected due to its sporadic nature and mild symptoms. However, recently, with its rapid spread from Asia to the Americas, affecting more than 30 countries, accumulating evidences have demonstrated a close association between infant microcephaly and Zika infection in pregnant women. Here, we reviewed the virological, epidemiological, and clinical essentials of ZIKV infection.展开更多
Dengue virus(DENV)is the most common mosquito-borne flavivirus,and it affects millions of people globally every year.Currently,there are no approved drugs for the treatment of dengue infection.By screening a natural p...Dengue virus(DENV)is the most common mosquito-borne flavivirus,and it affects millions of people globally every year.Currently,there are no approved drugs for the treatment of dengue infection.By screening a natural product library,we identified a novel compound,cyclovirobuxine D(Cvb D),that displays anti-DENV activity.Cvb D inhibits DENV replication in vitro in a dose-dependent manner and protects suckling mice against lethal DENV infection.Mechanistically,Cvb D regulates the expression of genes related to the cellular cholesterol pathway.As a result,Cvb D increases cellular cholesterol synthesis and accumulation,activates mTOR,and inhibits viral-dependent autophagy.Cvb D does not suppress autophagy initiation but impedes the nuclear translocation of the lysosome transcription factor TFEB.In addition,Cvb D restricts the replication of other positive-strand RNA viruses such as Zika virus and Coxsackievirus B3.We speculate that Cvb D could be a broad-spectrum antiviral drug candidate for use against positive-strand RNA viruses that require autophagy for optimal replication.展开更多
As a previously neglected member of flavivirus,Zika virus(ZIKV)has recently emerged and caused a global health concern because of its link to microcephaly and other congenital defects.Currently,no anti-ZIKV vaccine or...As a previously neglected member of flavivirus,Zika virus(ZIKV)has recently emerged and caused a global health concern because of its link to microcephaly and other congenital defects.Currently,no anti-ZIKV vaccine or therapy is commercially available.In this drug-screening study,tolvaptan,an FDA-approved drug,was identified to possess the activity against ZIKV strains of Asian lineage with low cytotoxicity using plaque and MTT assays.The anti-ZIKV activity of tolvaptan was also demonstrated using virus yield reduction assay and Western blotting analysis.Time-of-drug-addition assay showed that tolvaptan exerted its anti-ZIKV activity between 6 and 14 h post-ZIKV inoculation,concurrent with the post-entry events of ZIKV life cycle.Tolvaptan also exhibited inhibitory effects on ZIKV strains of African lineage,indicating that its anti-ZIKV activity was not strain dependent.Notably,tolvaptan could also reduce ZIKV-induced mortality in infected mice.Overall,these results suggested that tolvaptan was a potential therapeutic candidate against ZIKV that is worth further evaluation.展开更多
Tomato yellow leaf curl virus (TYLCV), belonging to the genus Begomovirus of the family Geminiviridae, is emerging as the most destructive pathogen of tomato plants. Since the first report of TYLCV in Shanghai, Chin...Tomato yellow leaf curl virus (TYLCV), belonging to the genus Begomovirus of the family Geminiviridae, is emerging as the most destructive pathogen of tomato plants. Since the first report of TYLCV in Shanghai, China in 2006, TYLCV has spread rapidly to 13 provinces or autonomous regions of China. In this study, the molecular varia- bility and evolution of TYLCV were monitored in Shanghai from its first upsurge in 2006 until 2010. Full-length genomic sequences of 26 isolates were obtained by rolling circle amplification. Sequence analysis showed that the intergenic region was the most variable, with a mean mutation rate of 4.81×10-3 nucleotide substitutions per site per year. Ge- netic differentiation was found within isolates obtained from 2006, 2009, and 2010, though a linear increase in genetic diversity over time was not evident. Whilst significant parts of TYLCV genes were under negative selection, the C4 gene embedded entirely within the C1 gene had a tendency to undergo positive selection. Our results indicate that a mechanism of independent evolution of overlapping regions could apply to the natural population of TYLCV in Shanghai, China.展开更多
文摘Objective:To investigate the inhibitory effect of curcumin on influenza virus HIN1 and H3N2 in vitro, Methods:The directly killing role of cureumin extract in vitro to influenza virus type A subtype H1N1 and H3N2 was evaluated by the canine kidney cells (MDCK), Results:The largest non toxic concentration of curcumin extract was 12, 5g/L and the effective inhibitory concentration to H1N1 and H3N2 was 6, 25G/1 AND 1,56g/L respectively, Conclusion: Curcumin extract have directly killing effect on H1N1 and H3N2 infections.
基金Supported by National Natural Science Foundation of China(30870109)~~
文摘[Objective]The aim of this study was to identify transient expression of movement protein (MP) gene in Nicotinana benthaminana rapidly and further investigate the function of this exogenous gene. [Method]The movement protein gene of barley yellow dwarf virus (BYDV) was cloned into potato virus X (PVX) viral vector of pGR107,and PVX-recombinant vector was obtained. After electroporation of Agrobacterium tumefaciens,PVX was inoculated into the lower leaves of tobacco by Agrobacterium infiltration assay to observe the infection of virus on tobacco. [Result]After infection for 7 days,upper non-inoculated leaves of tobacco infected by the PVX-recombinant vector showed the virus infection symptoms,while the control group had no viral infection phenomenon. Daily follow-up observations for two groups revealed that tobacco infected by PVX-recombinant vector had severe symptoms of virus infection and curling leaves,or even led to necrosis both in infiltrated and systemic leaves in late period. However,tobacco infected by PVX vector had only slight symptoms of virus infection and could recover from infection. RT-PCR of the infected tobacco indicated that exogenous gene BYDV-MP had a normal transcription and expression in tobacco. [Conclusion]As a determinant factor for viral disease,BYDV-MP promotes the systemic infection rate of PVX and its symptom. In addition,it is feasible to express exogenous MP gene in Nicotiana benthaminan via PVX expression vector.
基金Supported by the Key Project of National Natural Science Foundation of China, No. 39730380
文摘AIM: To assess the combinative role of aflatoxin B1 (AFB1), cyanobacterial toxins (cyanotoxins), and hepatitis B virus (HBV) x gene in hepatotumorigenicity. METHODS: One-week-old animals carrying HBV x gene and their wild-type littermates were intraperitoneally (ip) injected with either single-dose AFB1 [6 mg/kg body weight (bw)], repeated-dose cyanotoxins (microcystin- LR or nodularin, 10 μg/kg bw once a week for 15 wk), DMSO (vehicle control) alone, or AFB1 followed by cyanotoxins a week later, and were sacrificed at 24 and 52 wk post-treatment. RESULTS: AFB1 induced liver tumors in 13 of 29 (44.8%) transcjenic mice at 52 wk post-treatment, significantly more frequent than in wild-type mice (13.3%). This significant difference was not shown in the 24-wk study. Compared with AFB1 exposure alone, MC-LR and nodularin yielded approximately 3-fold and 6-fold increases in the incidence of AFB1-induced liver tumors in wild-type animals at 24 wk, respectively. HBV x gene did not further elevate the risk associated with coexposure to AFB1 and cyanotoxins. With the exception of an MC-LR-dosed wild-type mouse, no liver tumor was observed in mice treated with cyanotoxins alone at 24 wk. Neither DMSO-treated transgenic mice nor their wild-type littermates had pathologic alterations relevant to hepatotumorigenesis in even up to 52 wk. CONCLUSION: HBV x gene and nodularin promote the development of AFB1-induced liver tumors. Co-exposure to AFB1 and MC-LR tends to elevate the risk of liver tumors at 24 wk relative to exposure to one of them. The combinative effect of AFB1, cyanotoxins and HBVx on hepatotumorigenesis is weak at 24 wk.
基金supported by the National Science Foundation of China(Grant No.39930010)a NSFC Fund for Creative Research Groups(Grant No.30421002)to Wei Hua WU
文摘Although there were reports suggesting the involvement of endogenous cAMP in plant defense signaling cascades, there is no direct evidence supporting this notion yet and the detailed mechanism is unclear. In the present study, we have used pathogenic fungi Verticillium dahliae and Arabidopsis plants as a model system of plant-microb interaction to demonstrate the function of endogenous cAMP in Arabidopsis defense responses. Both V. dahliae inoculation and Verticillium toxins injection induced typical “wilt” symptoms in Arabidopsis seedlings. When either 8-Br-AMP (a membrane permeable cAMP analogue) or salicylic acid (SA) was applied to Arabidopsis, the plants became resistant to V. dahliae toxins. However, addition of 8-Br-AMP did not increase the resistance of Arabidopsis transgenic plants deficient in SA to the toxins, suggesting that cAMP might act upstream of SA in plant defense signaling pathway. Indeed, 8-Br-cAMP and forskolin, an activator of adenylyl cyclase, significantly stimulated the endogenous SA level in plants, whereas DDA, an inhibitor of adenylyl cyclase dramatically reduced toxin-induced SA increase. Both the endog- enous cAMP and SA increased significantly in Arabidopsis seedlings treated with toxins. Furthermore, transcription level of pathogenesis-related protein 1 gene (PR1) was strongly induced by both 8-Br-cAMP and the toxin treatment. Taken together, our data demonstrate that endogenous cAMP is involved in plant defense responses against Verticillium- secreted toxins by regulating the production of the known signal SA in plant defense pathway.
文摘Using mice infected with coxsackie B-3 virus (CVB3) as a viral myocarditis model, we observed the inhibitory effect of Astragalus membranaceus (AM) on CVB3-RNA replication in myocardial tissue of mice by RNA-RNA in situ hybridization with negative-strand RNA Probes labelled with  ̄(35)S and quantitative imaging analysis of positive signals. The mechanism of its effect on CVB3-RNA replication has been investigated by detection of beta-interferon (β-IFN) as well. Results showed that the copy numbers of CVB3-RNA as well as the histologic scores (necrosis) in myocardial tissues of infected-AM treated mice were significantly lower than those in infected and normal saline treated mice, suggesting that AM could inhibit the replication of CVB3-RVA,but its effect on CVB3-RNA replication had no correlation with induction of β-IFN.
文摘The cucumber mosaic virus (CMV) isolate P1 caused very mild symptoms on many plant species. After serial passages by mechanical inoculation over five years, CMV P1 caused severe symptoms on several tobacco cultivars and tomato. A specific band of approximately 0.3 kb in length was amplified by RT PCR with primers synthesized based on reported CMV satellite RNA (satRNA) sequences. Sequence analysis showed there were two satRNAs (Sat P1 1 and Sat P1 2). Sat P1 1 contained 335 nucleotides, and Sat P1 2 contained 394 nucleotides. These two satRNAs shared 64% overall nucleotide sequence homology, and differences between the two satRNAs included mutations as well as deletions. Sat P1 1 was identical to a satRNA (Z96099) reported in 1995 in CMV P1. Based on differences in the sequence and secondary structure between these two satRNAs, we conclude that Sat P1 2 represents the emergence of a new satellite (necrotic satellite) from attenuated satRNA populations. The possible effect of the emergence of this new satRNA is discussed.
文摘Dose-dependent IgY antibody response to different amounts oforthopox virus (OPV) antigen has been studied in immunized chickens for two different OPV strains (vaccinia virus, 7.0× 10^6 PFU and cowpox virus, 9.2× 10^7PFU). The antibody responses to different immunizations were tested and compared by indirect immunofluorescence antibody test. Our results, together with the literature, show that the antigen dose used for immunization plays an important role for the production of specific Abs. An increase in antigen concentration may achieve higher Ab titers but, dependent on the immunogenicity of OPV antigen, it can also lead to an immune depression. However, in this study we found that OPV played a positive correlation between antigen concentration and Ab-titer.
文摘AIM: To evaluate the anti-viral effect of emodin plus Astragalus polysaccharide (APS) in hepatitis B virus (HBV) transgenic mice.METHODS: Sixty HBV transgenic mice (HBV TGM) whose weight varied between 18 and 24 g were randomly divided into 3 groups, with 20 mice in each group. Group A was the normal control, where the mice were treated with physiological saline; group B was the positive control where the mice were treated with lamivudine solution (100 mL/kg per day). Group C was the experimental group where the mice were treated with physiological saline containing emodin and APS (57.59 mg/kg per day and 287.95 mg/kg per day, respectively). The mice were treated daily for 3 wk. After 1 wk recovery time, the mice were sacrifi ced and serum as well as liver tissues were collected for ELISA and histological examination.RESULTS: After 21 d treatment, HBV DNA levels in group B and group C significantly declined when compared with group A (P < 0.05). However, a signif icant increase in HBV DNA content was observed in group B, whereas this phenomenon was not observed in group C. A reduction in the contents of HBsAg, HBeAg and HBcAg in the mice from group B and C was observed when compared with group A.CONCLUSION: Emodin and APS have a weak but persistent inhibitory effect on HBV replication in vivo, which may function as a supplementary modality in the treatment of hepatitis B infection.
基金supported by the National Natural Science Foundations of China(81471957,81271839,81372935,81301435,and 81401676)
文摘An emerging mosquito-borne arbovirus named Zika virus(ZIKV), of the family Flaviviridae and genus Flavivirus, is becoming a global health threat. ZIKV infection was long neglected due to its sporadic nature and mild symptoms. However, recently, with its rapid spread from Asia to the Americas, affecting more than 30 countries, accumulating evidences have demonstrated a close association between infant microcephaly and Zika infection in pregnant women. Here, we reviewed the virological, epidemiological, and clinical essentials of ZIKV infection.
基金the Priority Academic Program Development of Jiangsu Higher Education InstitutionsProgram for Changjiang Scholars and Innovative Research Team in University(PCSIRT)+4 种基金the National Natural Science Foundation of China(31770933 and 81971917)the Natural Science Foundation of Colleges in Jiangsu Province(17KJA310005)the Open Project Fund from State Key Laboratory of Genetic Engineering,Fudan University(SKLGE1903)the Key Laboratory of Reproduction Regulation of NHC(KF2018-01)a grant from Soochow Securities。
文摘Dengue virus(DENV)is the most common mosquito-borne flavivirus,and it affects millions of people globally every year.Currently,there are no approved drugs for the treatment of dengue infection.By screening a natural product library,we identified a novel compound,cyclovirobuxine D(Cvb D),that displays anti-DENV activity.Cvb D inhibits DENV replication in vitro in a dose-dependent manner and protects suckling mice against lethal DENV infection.Mechanistically,Cvb D regulates the expression of genes related to the cellular cholesterol pathway.As a result,Cvb D increases cellular cholesterol synthesis and accumulation,activates mTOR,and inhibits viral-dependent autophagy.Cvb D does not suppress autophagy initiation but impedes the nuclear translocation of the lysosome transcription factor TFEB.In addition,Cvb D restricts the replication of other positive-strand RNA viruses such as Zika virus and Coxsackievirus B3.We speculate that Cvb D could be a broad-spectrum antiviral drug candidate for use against positive-strand RNA viruses that require autophagy for optimal replication.
基金National Key R&D Program of China(Grant No.2016YFC1201000)the Key Deployment Projects of the Chinese Academy of Sciences(Grant No.ZDRW-ZS-2016-4-2)the Key Laboratory of Bioactive Peptides of Yunnan Province(Grant No.AMHD-2017-3).
文摘As a previously neglected member of flavivirus,Zika virus(ZIKV)has recently emerged and caused a global health concern because of its link to microcephaly and other congenital defects.Currently,no anti-ZIKV vaccine or therapy is commercially available.In this drug-screening study,tolvaptan,an FDA-approved drug,was identified to possess the activity against ZIKV strains of Asian lineage with low cytotoxicity using plaque and MTT assays.The anti-ZIKV activity of tolvaptan was also demonstrated using virus yield reduction assay and Western blotting analysis.Time-of-drug-addition assay showed that tolvaptan exerted its anti-ZIKV activity between 6 and 14 h post-ZIKV inoculation,concurrent with the post-entry events of ZIKV life cycle.Tolvaptan also exhibited inhibitory effects on ZIKV strains of African lineage,indicating that its anti-ZIKV activity was not strain dependent.Notably,tolvaptan could also reduce ZIKV-induced mortality in infected mice.Overall,these results suggested that tolvaptan was a potential therapeutic candidate against ZIKV that is worth further evaluation.
基金supported by the Special Fund for Agro-Scientific Research in the Public Interest from the Ministry of Agriculture,China(No.201003065)the China Postdoctoral Science Foundation(No.2012M510200)the National Natural Science Foundation of China(No.31200117)
文摘Tomato yellow leaf curl virus (TYLCV), belonging to the genus Begomovirus of the family Geminiviridae, is emerging as the most destructive pathogen of tomato plants. Since the first report of TYLCV in Shanghai, China in 2006, TYLCV has spread rapidly to 13 provinces or autonomous regions of China. In this study, the molecular varia- bility and evolution of TYLCV were monitored in Shanghai from its first upsurge in 2006 until 2010. Full-length genomic sequences of 26 isolates were obtained by rolling circle amplification. Sequence analysis showed that the intergenic region was the most variable, with a mean mutation rate of 4.81×10-3 nucleotide substitutions per site per year. Ge- netic differentiation was found within isolates obtained from 2006, 2009, and 2010, though a linear increase in genetic diversity over time was not evident. Whilst significant parts of TYLCV genes were under negative selection, the C4 gene embedded entirely within the C1 gene had a tendency to undergo positive selection. Our results indicate that a mechanism of independent evolution of overlapping regions could apply to the natural population of TYLCV in Shanghai, China.